Chronic infection with hepatitis B virus (HBV) imparts a 40 percent lifetime risk of primary hepatocellular carcinoma (PHC) and a 15 percent risk of death from cirrhosis. At present, there is no safe effective treatment for either acute or chronic infection with HBV. Woodchucks chronically infected with woodchuck hepatitis virus (WHV) are a good "model" for chronic HBV infection in humans. They have a very high risk of developing PHC. In this project, woodchucks chronically infected with WHV will be used to test the hypothesis that woodchuck carriers of WHV treated with an extract of the tropical plant Phyllanthus amarus will have a significantly lower risk for primary hepatocellular carcinoma (PHC) than controls treated with placebo. Extracts of P. amarus inhibit the DNA polymerase of HBV, WHV and DHBV in vitro. In vivo, in recently infected carriers, the virus appears to be eliminated after treatment and does not return when treatment is stopped. In long-term carriers, the amount of cirus is markedly decreased following treatment. To contribute to a biological understanding of the phenomenon, in addition to the observations on development of PHC, measurements of the serological parameters of WHV infection, serological markers of early carcinogenesis (alpha fetoprotein, ferritin), and replicating forms of WHV DNA in liver tissues will be made. Based on estimates derived from our earlier studies, we calculated that 20 treated and 20 control animals will give significant power to test the hypothesis. They will be observed for 2 years; the total length of the project is 3 years. In previous papers and the grant application the plant from which the extract is derived was identified as P. niruru. It has now been re- classified as P. amarus.